5592
H. R. Lawrence et al. / Bioorg. Med. Chem. 18 (2010) 5576–5592
(M+H)+; HRMS (ES+) calculated for C19H18ClN2O4S (M+H)+
405.0670, found 405.0664.
11. Piva, R.; Ruggeri, B.; Williams, M.; Costa, G.; Tamagno, I.; Ferrero, D.; Giai, V.;
Coscia, M.; Peola, S.; Massaia, M.; Pezzoni, G.; Allievi, C.; Pescalli, N.; Cassin, M.;
di Giovine, S.; Nicoli, P.; de Feudis, P.; Strepponi, I.; Roato, I.; Ferracini, R.;
Bussolati, B.; Camussi, G.; Jones-Bolin, S.; Hunter, K.; Zhao, H.; Neri, A.;
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6.12.4. 2-Chloro-3-(3-(methylaminoperoxythio)phenylamino)
naphthalene-1,4-dione (13p)
Brown solid (0.28 g, 97%); mp: 229–230 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.52 (s, 1H disappeared on D2O shake), 8.04–8.02 (m,
2H), 7.82 (dt, J = 7.6, 1.2 Hz, 1H), 7.76 (dt, J = 7.6, 1.2 Hz, 1H),
7.53–7.45 (m, 4H changed to 3H on D2O shake), 7.35 (d,
J = 4.0 Hz, 1H), 2.79–2.76 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); LC–MS
(ES+) m/z 377.03 (M+H)+; HRMS (ES+) calculated for
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N.; Yip, R. M. L.; Sebti, S. M. Cell Cycle 2009, 8, 1940.
C
17H14ClN2O4S (M+H)+ 377.0357, found 377.0370.
16. Ahn, J. H.; Cho, S. Y.; Ha, J. D.; Chu, S. Y.; Jung, S. H.; Jung, Y. S.; Baek, J. Y.; Choi, I.
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1609.
6.12.5. 2-Chloro-3-(3-(ethylaminoperoxythio)phenylamino)
naphthalene-1,4-dione (13q)
Orange solid (0.193 g, 99%); mp: 239–240 °C decomposed; 1H
NMR (400 MHz, DMSO-d6) d 9.51 (s, 1H), 8.04–8.01 (m, 2H), 7.86
(dt, J = 7.6, 1.2 Hz, 1H), 7.81 (dt, J = 7.6, 1.2 Hz, 1H), 7.55 (t,
J = 5.6 Hz, 1H), 7.50–7.48 (m, 2H), 7.35–33 (m, 1H), 2.79–2.76 (m,
2H), 0.96 (t, J = 7.2 Hz, 3H); LC–MS (ESꢀ) m/z 389 (MꢀH)ꢀ; HRMS
(ESꢀ) calculated for
C
18H16ClN2O4S (MꢀH)ꢀ 389.0369, found
389.0371.
23. 70 ng of purified 20S rabbit proteasome was incubated with 20 lM Suc-Leu-
6.12.6. 2-Chloro-3-(3-(isopropylaminoperoxythio)
phenylamino)naphthalene-1,4-dione (13r)
Leu-Val-Tyr-AMC for the CT-L activity, Bz-Val-Gly-Arg-AMC for the T-L activity,
and benzyloxycarbonyl Z-Leu-Leu-Glu-AMC for the PGPH activity for 1 h at
Orange solid (0.64 g, 34%); mp: 211–212 °C; 1H NMR (400 MHz,
MeOH-d4) d 8.13 (dd, J = 3.2, 1.2 Hz, 1H), 8.12 (dd, J = 4.8, 1.6 Hz,
1H), 7.83 (dt, J = 9.2, 1.6 Hz, 1H), 7.77 (dt, J = 7.6, 1.2 Hz, 1H), 7.65
(ddd, J = 7.6, 2.0, 1.2 Hz, 1H), 7.56 (t, J = 1.6 Hz, 1H), 7.51 (t,
J = 8.0 Hz, 1H), 7.34 (ddd, J = 8.0, 2.4, 1.2 Hz, 1H), 3.32 (m, partially
overlapped with residual MeOH signal), 1.04 (d, J = 6.4 Hz, 6H); LC–
MS (ES+) m/z 405.07 (M+H)+; HRMS (ES+) calculated for
37 °C in 100 lL of assay buffer (50 mM Tris–HCl, pH 7.6) with or without
inhibitors. After incubation, production of hydrolyzed 7-amido-4-methyl-
coumarin (AMC) was measured using a WALLAC Victor2 1420 Multilabel
Counter with an excitation filter of 355 nm and an emission filter of 460 nm
(Perkin Elmer Life Sciences, Turku, Finland). The inhibitory activity of the
compounds was calculated based on vehicle control.
24. Groll, M.; Berkers, C. R.; Ploegh, H. L.; Ovaa, H. Structure (Cambridge, MA, US)
2006, 14, 451.
25. LigPrep, Version 2.2, Schrödinger, LLC, New York, 2005.
26. Shelley, J. C.; Cholleti, A.; Frye, L. L.; Greenwood, J. R.; Timlin, M. R.; Uchimaya,
M. J. Comput. Aided. Mol. Des. 2007, 21, 681.
C
19H18ClN2O4S (M+H)+ 405.0670, found 405.0664.
27. Cho, A. E.; Guallar, V.; Berne, B.; Friesner, R. A. J. Comput. Chem. 2005, 26,
915.
Acknowledgment
28. Dialysis using purified rabbit 20S proteasome: To measure the effect of dialysis
on CT-L activity, compounds (10 lM) or vehicle (0.1% DMSO) were added to
This work was supported by NIH Grant P01CA118210.
References and notes
rabbit 20S proteasome at a final concentration of 3 nM in proteasome assay
buffer (50 mM Tris–HCl, pH 7.6) and incubated at room temperature for
30 min. After 30 min of incubation, proteasome-compound mixtures were
added to 10,000 MWCO Thermo Scientific Slide-A-Lyzer Dialysis Cassette
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the dialysis cassette and the CT-L 20S proteasome activity was determined as
described in Ref. 23. Proteasome activity was normalized against proteasome
activity of DMSO control.
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